Cancer
Ingested nitrate and nitrite and incidence of thyroid cancer in the Agricultural Health Study Dazhe Chen* Dazhe Chen Christine G. Parks Laura E. Beane Freeman Jonathan N. Hofmann Rashmi Sinha Maya Spaur Jessica M. Madrigal Mary H. Ward Dale P. Sandler
Background: Nitrate and nitrite ingestion is associated with increased risk for some cancers, possibly via the endogenous formation of carcinogenic N-nitroso compounds. However, evidence on thyroid cancer (TC) is limited. We examined the associations of water nitrate and dietary nitrate and nitrite intakes with incident TC in the Agricultural Health Study. We also stratified analyses by sex, given the predominance of TC in women, and by vitamin C, an inhibitor of endogenous nitrosation.
Methods: We determined the primary drinking water source for participants at enrollment (1993-1997). For public water supply users with historical measurement data (N=14,779), we computed average nitrate concentrations in drinking water. For private well users (N=44,896), we developed random forest model estimates of nitrate concentrations based on well location, nitrogen inputs, and other predictors. Dietary nitrate and nitrite were assessed among the 29,371 participants who completed a diet history questionnaire at the first follow-up (1999-2003). Incident TC cases between study enrollment or first follow-up and 2021 were identified by linkage with Iowa and North Carolina cancer registries. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with incident TC overall and in strata of sex and vitamin C intake from foods and supplements.
Results: We identified 192 TC cases (77 for dietary analyses). Water nitrate and dietary nitrate/nitrite were not associated with TC overall. We found a positive association between water nitrate and TC in women (N=25,356; T2 vs. T1 HR: 1.37, 95%CI: 0.86, 2.21; T3 vs. T1 HR: 1.44, 95%CI: 0.91, 2.26) but not men. We also found elevated HRs (>1.50) in upper tertiles of water nitrate and dietary nitrite exposures in those with vitamin C <median, although exposure-response trends were not monotonic.
Conclusion: Water nitrate and dietary nitrite intakes may increase the incidence of TC among women.